title: Direct delivery of functional proteins and enzymes to the cytosol using nanoparticle-stabilized nanocapsules.
abstract: Intracellular protein delivery is an important tool for both therapeutic and fundamental applications. Effective protein delivery faces two major challenges: efficient cellular uptake and avoiding endosomal sequestration. We report here a general strategy for direct delivery of functional proteins to the cytosol using nanoparticle-stabilized capsules (NPSCs). These NPSCs are formed and stabilized through supramolecular interactions between the nanoparticle, the protein cargo, and the fatty acid capsule interior. The NPSCs are ~130 nm in diameter and feature low toxicity and excellent stability in serum. The effectiveness of these NPSCs as therapeutic protein carriers was demonstrated through the delivery of fully functional caspase-3 to HeLa cells with concomitant apoptosis. Analogous delivery of green fluorescent protein (GFP) confirmed cytosolic delivery as well as intracellular targeting of the delivered protein, demonstrating the utility of the system for both therapeutic and imaging applications.
authors.affiliation: Department of Chemistry, University of Massachusetts-Amherst, 710 North Pleasant Street, Amherst, Massachusetts, 01003, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Tang
authors.affiliation: Department of Chemistry, University of Massachusetts-Amherst, 710 North Pleasant Street, Amherst, Massachusetts, 01003, USA.
authors.forename: Chang Soo
authors.initials: CS
authors.lastname: Kim
authors.affiliation: Department of Chemistry, University of Massachusetts-Amherst, 710 North Pleasant Street, Amherst, Massachusetts, 01003, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Solfiell
authors.affiliation: Department of Chemistry, University of Massachusetts-Amherst, 710 North Pleasant Street, Amherst, Massachusetts, 01003, USA.
authors.forename: Subinoy
authors.initials: S
authors.lastname: Rana
authors.affiliation: Department of Chemistry, University of Massachusetts-Amherst, 710 North Pleasant Street, Amherst, Massachusetts, 01003, USA.
authors.forename: Rubul
authors.initials: R
authors.lastname: Mout
authors.affiliation: Department of Chemistry, University of Massachusetts-Amherst, 710 North Pleasant Street, Amherst, Massachusetts, 01003, USA.
authors.forename: Elih M
authors.initials: EM
authors.lastname: Velázquez-Delgado
authors.affiliation: Department of Chemistry, University of Massachusetts-Amherst, 710 North Pleasant Street, Amherst, Massachusetts, 01003, USA.
authors.forename: Apiwat
authors.initials: A
authors.lastname: Chompoosor
authors.affiliation: Department of Chemistry, University of Massachusetts-Amherst, 710 North Pleasant Street, Amherst, Massachusetts, 01003, USA.
authors.forename: Youngdo
authors.initials: Y
authors.lastname: Jeong
authors.affiliation: Department of Chemistry, University of Massachusetts-Amherst, 710 North Pleasant Street, Amherst, Massachusetts, 01003, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Yan
authors.affiliation: Department of Chemistry, University of Massachusetts-Amherst, 710 North Pleasant Street, Amherst, Massachusetts, 01003, USA.
authors.forename: Zheng-Jiang
authors.initials: ZJ
authors.lastname: Zhu
authors.affiliation: Department of Chemistry, University of Massachusetts-Amherst, 710 North Pleasant Street, Amherst, Massachusetts, 01003, USA.
authors.forename: Chaekyu
authors.initials: C
authors.lastname: Kim
authors.affiliation: Department of Chemistry, University of Massachusetts-Amherst, 710 North Pleasant Street, Amherst, Massachusetts, 01003, USA.
authors.forename: Jeanne A
authors.initials: JA
authors.lastname: Hardy
authors.affiliation: Department of Chemistry, University of Massachusetts-Amherst, 710 North Pleasant Street, Amherst, Massachusetts, 01003, USA.
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Rotello
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000737:chemistry*; D003593:Cytoplasm / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry*; D011992:Endosomes / Q000378:metabolism; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D053769:Nanocapsules / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D008024:Ligands; D053769:Nanocapsules; D011506:Proteins; D049452:Green Fluorescent Proteins; D053148:Caspase 3